Journal Article

Chemical inactivation of two non-enveloped viruses results in distinct thermal unfolding patterns and morphological alterations

Banerjee, Manidipa, Narula, Pankhuri, Pathak, Sandip B., Mukherjee, Sayandip, Lokshman, Milan Kumar

2024

Overview

Background Non-enveloped viruses, which lack a lipid envelope, display higher resistance to disinfectants, soaps and sanitizers compared to enveloped viruses. The capsids of these viruses are highly stable and symmetric protein shells that resist inactivation by commonly employed virucidal agents. This group of viruses include highly transmissible human pathogens such as Rotavirus, Poliovirus, Foot and Mouth Disease Virus, Norovirus and Adenovirus; thus, devising appropriate strategies for chemical disinfection is essential. Results In this study, we tested a mild, hypoallergenic combination of a denaturant, alcohol, and organic acid (3.2% citric acid, 1% urea and 70% ethanol, pH4) on two representative non-enveloped viruses – Human Adenovirus 5 (HAdV5) and Feline Calicivirus (FCV)– and evaluated the pathways of capsid neutralization using biophysical methods. The conformational shifts in the capsid upon chemical treatment were studied using Differential Scanning Calorimetry (DSC), while the morphological alterations were visualized concurrently using Transmission Electron Microscopy (TEM). We found that while treatment of purified HAdV5 particles with a formulation resulted in thermal instability and, large scale aggregation; similar treatment of FCV particles resulted in complete collapse of the capsids. Further, while individual components of the formulation caused significant damage to the capsids, a synergistic action of the whole formulation was evident against both non-enveloped viruses tested. Conclusions The distinct effects of the chemical treatment on the morphology of HAdV5 and FCV suggests that non-enveloped viruses with icosahedral geometry can follow different morphological pathways to inactivation. Synergistic effect of whole formulation is more effective compared to individual components. Molecular level understanding of inactivation pathways may result in the design and development of effective mass-market formulations for rapid neutralization of non-enveloped viruses.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Acids / Adenovirus / Adenoviruses / Adenoviruses, Human - chemistry / Adenoviruses, Human - drug effects / Adenoviruses, Human - physiology / Adenoviruses, Human - ultrastructure / Analysis / Animals / Antiviral agents / Biological Microscopy / Biomedical and Life Sciences / Calicivirus, Feline - drug effects / Calicivirus, Feline - physiology / Calorimetry / Calorimetry, Differential Scanning / Capsid - chemistry / Capsid - drug effects / Capsid - ultrastructure / Capsid Proteins - chemistry / Capsid Proteins - metabolism / Capsids / Care and treatment / Chemical damage / Chemical inactivation / Chemical treatment / Citric acid / Citric Acid - chemistry / Citric Acid - pharmacology / Deactivation / Diagnosis / Differential scanning calorimetry / Disease resistance / Disease susceptibility / Disinfectants / Disinfectants - pharmacology / Dosage and administration / Ethanol / Ethanol - pharmacology / Feline calicivirus / Foot & mouth disease / Heat treatment / Human adenovirus / Humans / Inactivation / Infections / Life Sciences / Lipids / Microbiology / Microscopy / Microscopy, Electron, Transmission / Morphology / Mycology / Neutralization / Non-enveloped viruses / Norovirus / Organic acids / Pandemics / Parasitology / Proteins / Rotavirus / Sanitizers / Soap / Soaps / Synergistic effect / Thermal instability / Thermal resistance / Transmission electron microscopy / Urea / Urea - analogs & derivatives / Urea - chemistry / Urea - pharmacology / Virology / Virus diseases / Virus Inactivation - drug effects / Viruses